Table 2.

Pharmacokinetic studies of diuretics in patients with heart failure and controls

Drug, dose, route of administration, reference	Study group, size, NYHA class, age and sex	Renal disease *	Hepatic disease *	F	C max	C ss	T max	V D	CL	t 1/2	AUC
Bumetanide, 3 mg, oral and i.v. 51	HF: n = 6, NYHA III‐IV, age 60 ± 12 years, 5M/1FC: n = 4, age 30 ± 7 years, 4M/0F	Yes	No	→	→	n/a	→	→	→a↓ (−44%)	→	n/a
Bumetanide, 1‐2 mg, oral 53	HF: n = 20, NYHA I‐IV, age 33–74 years, 14M/4FC: n = 10, age n/a, 10M/0F	Yes	n/a	n/a	n/a	n/a	n/a	n/a	n/a	↑ (+144%)	n/a
Furosemide, 40–80 mg, oral 53	HF: n = 20, NYHA I‐IV, age 33–74 years, 14M/4FC: n = 10, age n/a, 10M/0F	Yes	n/a	n/a	n/a	n/a	n/a	n/a	n/a	↑ (+70%)	n/a
Furosemide, 40 mg, oral and i.v. 52	HF: n = 17, NYHA, age and M/F n/aC: n = 8, age 22–27 years, 5M/3F	Yes	n/a	→	n/a	n/a	n/a	→	→	→	n/a
Furosemide, 40 mg, i.v. 38	HF: n = 6, NYHA n/a, age 69 ± 24 years, M/F n/aC: n = 8, age 52 years, 6M/2F	No	n/a	n/a	n/a	n/a	n/a	→	↓ (−50%)	→	n/a
Hydroflumethiazide, 25 mg, oral 39	HF: n = 9, NYHA I‐III, age 65 ± 11 years, 9M/0FC: n = 5, age 29 ± 1 years, 4M/1F	No	n/a	n/a	n/a	n/a	n/a	↓ (−52%)	→	↓ (−42%)	→
Metolazone, 2.5 mg, oral 40	HF: n = 3, NYHA and age n/a, 2M/1FC: n = 3, age n/a, 3M/0F	No	n/a	n/a	n/a	n/a	n/a	n/a	→	n/a	n/a

AUC, area under the curve; C: controls; CL, clearance; C _max, maximum plasma/serum concentration; C _ss, concentration at steady state; F, bioavailability; F, female; HF, patients with heart failure; M, male; n/a not available/reported; NYHA, New York Heart Association functional class; T _max, time to reach the maximum plasma/serum concentration; t _1/2, elimination half‐life; V_D, volume of distribution;

^* , significant; ↑, significantly increased; ↓, significantly decreased; →, not statistically different;

^a No significant differences in clearance between heart failure patients and controls after i.v. dose, clearance in heart failure patients was significantly lower than controls after oral dose;

^b no statistical analysis reported